Summary of Work: Rates of spontaneous mutation vary greatly among organisms. We have previously described several genomic mutation rates that are characteristic of certain broad groups of organisms. (1) The characteristic mutation rate for DNA-based microbes is about 0.003 per genome replication. In the Archeon Sulfolobus acidocaldarius growing at 75 degrees C, the mutation rate is close to 0.003 but the proportion of base-pair substitutions is lower than in all other DNA-based organisms. We hypothesized that the average missense mutation has a greater deleterious effect at high temperatures. As a result, evolutionary pressures would act to decrease base-substitution mutation rates. One prediction of this hypothesis is that the ratio of missense to silent (synonymous) mutations accumulating in the course of evolution would be lower in thermophiles than in mesophiles. Another prediction is that a thermophilic eubacterium would also show reduced frequencies of base-pair substitutions but that a mesophilic archaeon would not. These predictions are now being tested. (2) The first mutational spectrum for a ribovirus has been obtained using tobacco mosaic virus growing in a host carrying a TMV transgene that complements defects in the 804-base gene that facilitates the spread of virus particles between cells. The most remarkable aspect of the spectrum is the high proportion of mutants carrying multiple mutations, far in excess of predictions based on the mutant frequency. The results suggest that nonheritable, transitory hypermutability contributes strikingly to mutation in this ribovirus.